LUNG EPITHELIAL TRANSPORT PROPERTIES AND ALVEOLAR EDEMA

拟议研究的目标是研究 主动水与被动水的特性及调控 溶质跨肺泡上皮屏障的运输， 并了解它们在肺泡动态平衡中的作用 水肿症。我们将用两个例子来研究这些传输性质 制备分离的肺泡上皮，除 灌流的大鼠肺上皮细胞完整。总的前提是 我们的节目是关于特征和信息的 水和溶质跨肺泡运输的调节 上皮细胞将导致进一步的洞察，不仅是对基本的 这种组织屏障的功能，也成了重要的 这种输运性质在产生和去除 正常和异常情况下的肺泡液。这个 调查将采取多管齐下的方法，利用 两种分离的上皮制备物(哺乳动物肺泡 原代培养的上皮细胞和空心肺 两栖动物)，以生成有关运输的基本信息 穿过肺泡上皮屏障。哺乳动物II型细胞 将主要作为多孔表面的单层进行研究，以及 两栖动物的肺将作为囊和平板进行研究。 在这些基本调查中产生的信息将是 与研究完整的 哺乳动物肺灌流的肺泡上皮细胞。特定的 这些制剂的被动输运特性研究 将包括测定被动溶质渗透率、水 流体静压和/或渗透压梯度产生的通量，以及 通过肺泡上皮运输的途径。主动型 交通研究将包括生物电学的测量 属性(包括自发电位差、组织 电阻和短路电流)、活性离子(钠)通量， 以及由于活跃的溶质运移而引起的水的运动。 研究物理化学参数(例如， 温度、pH)、药剂(例如，激素)，以及 尤其是肺损伤(例如，由氧化剂引起)构成了 这项提议。预计我们的调查将提供 对肺泡运输特性的进一步认识 正常和异常成年哺乳动物肺的上皮屏障， 以及这些屏障特性在正常肺泡中的作用 体内动态平衡与肺泡性肺水肿。

The goals of the proposed research are to study the characteristics and regulation of active and passive water and solute transport across the pulmonary alveolar epithelial barrier, and to understand their roles in alveolar homeostasis and edemagenesis. We will study these transport properties using two preparations of isolated alveolar epithelium, in addition to the intact epithelium of the perfused rat lung. The overall premise of our program is that information about the characteristics and regulation of the transport of water and solutes across alveolar epithelium will lead to further insight not only into the basic functions of this tissue barrier, but also into the importance of such transport properties in the generation and removal of alveolar fluid under normal and abnormal conditions. The investigations will follow a multi-pronged approach of utilizing the two isolated epithelial preparations (mammalian alveolar epithelial cells in primary culture, and the hollow lungs of amphibians) to generate fundamental information about transport across the alveolar epithelial barrier. Mammalian type Ii cells will be studied primarily as monolayers n porous surfaces, and amphibian lungs will be studied as sacs and flat sheets. Information generated in these basic investigations will be compared to that from studies of transport across the intact alveolar epithelium of the perfused mammalian lung. Specific studies of the passive transport properties of these preparations will include determination of passive solute permeabilities, water flux due to hydrostatic and/or osmotic pressure gradients, and pathways for transport across the alveolar epithelium. Active transport studies will include measurements of bioelectric properties (including spontaneous potential difference, tissue resistance and short circuit current), active ion (sodium) fluxes, and water movements due to active solute transport. Investigation of the effects of physiocochemical parameters (e.g., temperature, pH), pharmacological agents (e.g., hormones), and especially lung injury (e.g., by oxidants) constitute a major part of this proposal. It is anticipated that our investigations will provide further insight into the transport characteristics of the alveolar epithelial barrier in normal and abnormal adult mammalian lungs, and into the roles of these barrier properties in normal alveolar homeostasis and alveolar pulmonary edema in vivo.